{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T13:58:19Z","timestamp":1787752699615,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T00:00:00Z","timestamp":1664323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["EMCR 2013\u20106080"],"award-info":[{"award-number":["EMCR 2013\u20106080"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["EMCR 2014\u20106780"],"award-info":[{"award-number":["EMCR 2014\u20106780"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Severe congenital neutropenia (SCN) patients are prone to develop myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML). Leukaemic progression of SCN is associated with the early acquisition of <jats:italic>CSF3R<\/jats:italic> mutations in haematopoietic progenitor cells (HPCs), which truncate the colony\u2010stimulating factor 3 receptor (CSF3R). These mutant clones may arise years before MDS\/AML becomes overt. Introduction and activation of CSF3R truncation mutants in normal HPCs causes a clonally dominant myeloproliferative state in mice treated with CSF3. Paradoxically, in SCN patients receiving CSF3 therapy, clonal dominance of CSF3R mutant clones usually occurs only after the acquisition of additional mutations shortly before frank MDS or AML is diagnosed. To seek an explanation for this discrepancy, we introduced a patient\u2010derived CSF3R\u2010truncating mutation in ELANE\u2010SCN and HAX1\u2010SCN derived and control induced pluripotent stem cells and compared the CSF3 responses of HPCs generated from these lines. In contrast to <jats:italic>CSF3R\u2010<\/jats:italic>mutant control HPCs, <jats:italic>CSF3R\u2010<\/jats:italic>mutant HPCs from SCN patients do not show increased proliferation but display elevated levels of inflammatory signalling. Thus, activation of the truncated CSF3R in SCN\u2010HPCs does not evoke clonal outgrowth but causes a sustained pro\u2010inflammatory state, which has ramifications for how these CSF3R mutants contribute to the leukaemic transformation of SCN.<\/jats:p>","DOI":"10.1111\/bjh.18477","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T08:39:33Z","timestamp":1664354373000},"page":"79-86","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Truncated <scp>CSF3<\/scp> receptors induce pro\u2010inflammatory responses in severe congenital neutropenia"],"prefix":"10.1111","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6100-9290","authenticated-orcid":false,"given":"Patricia A.","family":"Olofsen","sequence":"first","affiliation":[{"name":"Department of Hematology Erasmus University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis A.","family":"Bosch","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans W. 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